6-(Arylhydrazino)pyrimidines are the only class of drugs known to react specifically with and inhibit a replication-specific DNA polymerase. My primary objectives are: 1) to characterize in detail -through the synthesis of reversible and irreversible inhibitor analogs and the study of structure-activity relationships with wild-type and mutant enzymes - the mechanism by which these compounds react with the inhibitor-specific site of DNA polymerase III of B. subtilis, and 2) to identify - by the screening of structural variants of the arylhydrazino-pyrimidines - specific derivatives which will selectively inhibit other, naturally resistant, DNA polymerases from prokaryotic and eukaryotic organisms. The long range goal of this program is to produce polymerase-specific reagents which will facilitate the identification and characterization of polymerases from a wide spectrum of organisms, and which can be exploited to attack DNA polymerases whose functions are critical to the pathogenesis of infectious and neoplastic diseases.